title: Adenovirus-mediated gene transfer into cold-preserved liver allografts: survival pattern and unresponsiveness following transduction with CTLA4Ig.
abstract: The immune response of liver transplant recipients was modulated via adenovirus-mediated transduction of the cold-preserved liver with sequences encoding CTLA4Ig. Transplanted allografts demonstrated rapid transient local expression and recombinant protein production shortly after revascularization, resulting in intact liver function, indefinite survival of the recipient, and the development of donor-specific unresponsiveness. Lymphocytic infiltration of the graft was mainly of the T helper 2 (Th2) subset and was not associated with injury to primary cellular targets of the alloimmune response. These findings demonstrate a successful outcome of a feasible and potentially clinically relevant system of gene delivery of sequences encoding proteins capable of inhibiting the alloimmune response.
authors.affiliation: Department of Surgery, University of Pennsylvania, Philadelphia 19104, USA. kolthoff@mail.med.upenn.edu
authors.forename: K M
authors.initials: KM
authors.lastname: Olthoff
authors.forename: T A
authors.initials: TA
authors.lastname: Judge
authors.forename: A E
authors.initials: AE
authors.lastname: Gelman
authors.forename: X
authors.initials: X
authors.lastname: da Shen
authors.forename: W W
authors.initials: WW
authors.lastname: Hancock
authors.forename: L A
authors.initials: LA
authors.lastname: Turka
authors.forename: A
authors.initials: A
authors.lastname: Shaked
mesh_terms: D000069594:Abatacept; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics* / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D060908:CTLA-4 Antigen; D015925:Cryopreservation; D018014:Gene Transfer Techniques; D006085:Graft Survival; D018796:Immunoconjugates; D008099:Liver / Q000502:physiology; D016031:Liver Transplantation / Q000276:immunology / Q000379:methods*; D010477:Perfusion; D051381:Rats; D011912:Rats, Inbred ACI; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; D018796:Immunoconjugates; D011993:Recombinant Fusion Proteins; D000069594:Abatacept; D001219:Aspartate Aminotransferases